This renewal proposal describes an interdisciplinary, systematic and targeted study of Peruvian plants with cicatrizant (wound-healing) activity. Although cicatrizant plants constitute the main focus of this proposal, extracts will also be screened for potential antineoplasic activity. The diverse topography, semitropical climate and unique cultural heritage of Peru contribute to making this country a desirable place for bioprospecting. Cicatrizant agents could help patients with illness such as diabetes, gastric ulcers or varicose ulcers, whose wounds do not scar easily. Notwithstanding these medical benefits, the scientific study of wound-healing plants may help uncover whether a connection can be established between injuries, healing and the treatment of proliferative disorders. Recent work has uncovered evidence that strengthens a correlation between injury and carcinogenesis. The study of cicatrizant plants and the mechanisms by which their active principle(s) operate, will reveal natural agents capable of promoting tissue regeneration. This investigation will shed light on externally promoted healing mechanisms triggered by acute and, perhaps chronic, injury. A five-step approach to wound-healing natural products has been designed: 1. Characterization of the active principle from Anredera diffusa and bioassay-guided fractionation of Jatropa curcas latex. The former was isolated during the previous grant period. 2. Structure-activity relationship studies on taspine and (+)-anymol, the two cicatrizant principles found in Croton lechleri and Peperomia galioides, respectively. The latter was isolated and identified during the previous grant period. 3. Cell migration and cell proliferation studies to probe mechanism of action for cicatrizant principles found in Peperomia galioides, Anredera diffusa and Jatropa curcas. 4. Characterization of the active principle from an extract who failed to show in vivo wound-healing activity during the previous grant period but tested positive in our anticancer screening assay. This corresponds to a potential topoisomerase II inhibitor from Campsiandra angustifolia. 5. Scientific evaluation of crude extracts from newly identified Peruvian plants with cicatrizant and anticancer activity. The long-term objective of this research is to strengthen the international and multidisciplinary collaboration between scientists from Peru and the United States, with the aim of linking conservation of biological diversity with sustained economic management of medicinal plants needed for the discovery and development of pharmaceuticals to improve human health.